“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Multidrug-resistant TB infections are becoming more common. A failure to identify drug resistance is bad for individual patients, and facilitates the wider spread of drug-resistant bacteria.

Culturing TB bacteria to assess resistance is technically difficult and can take up to four months. Molecular diagnostics are increasingly being used, but do not necessarily identify all resistance mutations.

The DIAMA study is evaluating new options that could provide more rapid results on drug resistance than culturing. It builds on previous EDCTP funding and an infrastructure that undertakes continuous monitoring of TB patients for resistance to rifampicin.

Benin and Rwanda have established reference laboratories that can use the ‘Deeplex’ assay, which generates sequence information on genes conferring resistance to 14 key anti-TB drugs. In the first phase of the study, sputum samples will be shipped to the reference labs for Deeplex analysis and results compared with those obtained by the traditional culturing method.

In the second phase of the study, all participating countries will begin using two lower-tech tools – Molbio Diagnostics’ TrueNat test and the latest version of the Xpert molecular diagnostic platform – which do not require samples to be sent to a reference laboratory. Results will be compared with those obtained by Deeplex analysis. Newly developed software will be used to transmit results immediately to national TB programmes. Use of the new tools in patient management will be evaluated at two pilot sites. The project will also explore use of two faster alternatives to culture to monitor responses to treatment.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

Use of the new approaches could lead to more rapid identification of multidrug-resistant TB, and dramatically improve treatment in resource-poor settings, where treatment outcomes are typically much worse than in high-income countries.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact